Dataset Information

Effect of MALAT1 Polymorphisms on Papillary Thyroid Cancer in a Chinese Population.

ABSTRACT: Background: Long noncoding RNA MALAT1 has been previously reported in the carcinogenesis of several tumors, and its potential functional polymorphisms have also been investigated in various diseases. However, the relationship between these polymorphisms and the susceptibility of thyroid cancer has still been largely unknown. In the present study, we aimed to explore the association between MALAT1 polymorphisms and thyroid cancer (TC) susceptibility, as well as potential biological function in TC. Methods: We conducted a case-control study with 1134 papillary thyroid cancer (PTC) patients and 1228 controls to evaluate the potential correlation between MALAT1 genetic variations (single nucleotide polymorphism, SNP) and the risk of PTC. More detailed molecular mechanisms were explored by luciferase assay, cell counting kit-8 (CCK-8), and flow cytometry. Results: MALAT1 SNP rs619586 was identified as a significantly protective factor of PTC susceptibility (P = 0.017, OR= 0.76, 95%CI = 0.60-0.95). Further functional experiments of rs619586 indicated that G allele of rs619586 could significantly decrease MALAT1expression, reduce PTC proliferation, and directly increase PTC apoptosis. Conclusions: Our findings suggested that MALAT1 SNP rs619586 could serve as a potential indicator for PTC susceptibility and pathogenesis.

SUBMITTER: Wen J

PROVIDER: S-EPMC6879318 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Effect of MALAT1 Polymorphisms on Papillary Thyroid Cancer in a Chinese Population.

Wen Jing J Chen Liang L Tian Hua H Li Ji J Zhang Miao M Cao Qing Q Zhang Wei W Chen Shi S Shi Lixin L

Journal of Cancer 20190919 23

<b>Background:</b> Long noncoding RNA MALAT1 has been previously reported in the carcinogenesis of several tumors, and its potential functional polymorphisms have also been investigated in various diseases. However, the relationship between these polymorphisms and the susceptibility of thyroid cancer has still been largely unknown. In the present study, we aimed to explore the association between MALAT1 polymorphisms and thyroid cancer (TC) susceptibility, as well as potential biological functio ...[more]

PMID: 31788131

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Project description:Several studies have reported the association between MAPK signaling pathway gene polymorphisms and papillary thyroid carcinoma (PTC). KRAS gene, an oncogene from the mammalian RAS gene family plays an important role in the MAPK pathway. This study aimed to identify the potential association of KRAS gene polymorphisms with susceptibility to PTC in a Han Chinese population. A total of 861 patients with PTC, 562 disease controls with nodular goiter and 897 healthy controls were recruited. Four tagSNP polymorphisms (rs12427141, rs712, rs7315339 and rs7960917) of KRAS gene were genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Statistical analyses and haplotype estimations were conducted using Haploview and Unphased softwares. Only significant differences were observed in genotypic frequencies of the rs7315339 polymorphism (χ2 =7.234, df=2, p=0.027) between PTC and disease controls. Statistically significant differences in both allelic and genotypic genotypes frequencies for rs712 (Genotype, χ2=8.258, p=0.016) and rs12427141 (Allele, χ2=3.992, p=0.046; Genotype, χ2=8.140, p=0.017) were observed between PTC patients and controls. Haplotype analyses revealed higher frequencies of GA and TA haplotypes (p=0.039 and p=0.003, respectively) from rs712- rs12427141 (two-SNP) or TGA and TTG haplotype containing the alleles from rs7960917, rs712 and rs12427141, as well as the GAT haplotype containing the alleles from rs712, rs12427141 and rs7315339 in PTC patients than in healthy controls (p=0.042, p=0.037, p=0.027, respectively). Inversely, the haplotype TTA from rs7960917, rs712 and rs12427141 or the haplotype TAC from rs712, rs12427141 and rs7315339 was significantly less frequent in the PTC patients than in normal control (p=0.003, p=0.003, respectively). These findings suggest the role of these KRAS gene variants in susceptibility to PTC. Moreover, significant differences of the KRAS gene polymorphisms may occur between nodular goiter and PTC.

Project description:OBJECTIVES:Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer, which accounts for 80-90% of all thyroid cancer cases. Though the pathological mechanism hasn't been fully understood, it is reported that both environmental and genetic factor may contribute to the PTC susceptibility. MicroRNAs (miRNAs) are small non-coding RNA molecules which function as the suppressors to participate in a variety of biological processes. Accumulating evidence suggests that polymorphisms of miRNAs were associated with the tumorigenesis of various cancers, including PTC. In this article, we focus on the association between four common microRNA polymorphisms (miR-146a, miR-608, miR-933, and miR-149) and PTC risk in a Han Chinese population. METHODS:In this case-control study, we recruited 1,398 participants in total, including 369 PTC patients, 278 patients with thyroid benign nodules (BN) and 751 normal controls. The miRNAs polymorphisms were genotyped and analyzed by using MALDI-TOF mass spectrometry. The odd ratios and their 95% confidence interval (95% CI) were calculated to evaluate the association between miRNAs polymorphisms and PTC risk. Furthermore, a meta-analysis based on previous studies was conducted to comprehensively assess the diagnostic performance of miR-146a in the PTC diagnosis. RESULTS:The miR-146a polymorphisms were shown to be significantly correlated with elevated risk of PTC under the heterozygous, homozygous, dominant and allelic models by comparing the genotype distribution between PTC cases and healthy controls, as well as between PTC cases and BN cases. However, the result of meta-analysis showed no significant association between miR-146a polymorphisms and PTC risk. CONCLUSIONS:Our study indicated that the miR-146a polymorphism was significantly associated with PTC risk. In contrast, meta-analysis revealed no evidence of association between miR-146a variants and PTC risk. Further studies are required to elucidate the role of miR-146a in the etiology of PTC.

Dataset Information

Effect of MALAT1 Polymorphisms on Papillary Thyroid Cancer in a Chinese Population.

Publications

Effect of MALAT1 Polymorphisms on Papillary Thyroid Cancer in a Chinese Population.

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